Gammagard

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Gammagard

INDICATIONS

GAMMAGARD S/D (immune globulin) is not indicated in patients with selective IgA deficiency where
the IgA deficiency is the only abnormality of concern (see WARNINGS).

Primary Immunodeficiency Diseases

GAMMAGARD S/D (immune globulin) is indicated for the treatment of primary immunodeficient states,
such as: congenital agammaglobulinemia, common variable immunodeficiency, Wiskott-Aldrich
syndrome, and severe combined immunodeficiencies.6,7 This indication
was supported by a clinical trial of 17 patients with primary immunodeficiency
who received a total of 341 infusions. GAMMAGARD S/D (immune globulin) is especially useful when
high levels or rapid elevation of circulating IgG are desired or when intramuscular
injections are contraindicated (e.g., small muscle mass).

B-cell Chronic Lymphocytic Leukemia (CLL)

GAMMAGARD S/D (immune globulin) is indicated for prevention of bacterial infections in patients
with hypogammaglobulinemia and/or recurrent bacterial infections associated
with B-cell Chronic Lymphocytic Leukemia (CLL). In a study of 81 patients, 41
of whom were treated with GAMMAGARD, Immune Globulin Intravenous (Human), bacterial
infections were significantly reduced in the treatment group.8,9
In this study, the placebo group had approximately twice as many bacterial infections
as the IGIV group. The median time to first bacterial infection for the IGIV
group was greater than 365 days. By contrast, the time to first bacterial infection
in the placebo group was 192 days. The number of viral and fungal infections,
which were for the most part minor, was not statistically different between
the two groups.

Idiopathic Thrombocytopenic Purpura (ITP)

When a rapid rise in platelet count is needed to prevent and/or to control
bleeding in a patient with Idiopathic Thrombocytopenic Purpura, the administration
of GAMMAGARD S/D (immune globulin) , should be considered.

The rise in platelet count to greater than 40,000/mm3 occurred after
a single 1 g/kg infusion of GAMMAGARD (immune globulin) in 8 patients with chronic ITP (6 adults,
2 children), and in 2 patients with acute ITP (one adult, one child). A similar
response was observed after two 1 g/kg infusions in 3 adult patients with chronic
ITP, and one child with acute ITP. The remaining 2 adult patients with chronic
ITP received more than two 1 g/kg infusions before achieving a platelet count
greater than 40,000/mm3. The rise in platelet count was generally rapid, occurring
within 5 days. However, this rise was transient and not considered curative.
Platelet count rises lasted 2 to 3 weeks, with a range of 12 days to 6 months.
It should be noted that childhood ITP may resolve spontaneously without treatment.

Kawasaki Syndrome

GAMMAGARD S/D (immune globulin) , is indicated for the prevention of coronary artery aneurysms
associated with Kawasaki syndrome. The percentage incidence of coronary artery
aneurysm in patients with Kawasaki syndrome receiving GAMMAGARD (immune globulin) either at a
single dose of 1 g/kg (n=22) or at a dose of 400 mg/kg for four consecutive
days (n=22), beginning within seven days of onset of fever, was 3/44 (6.8%).
This was significantly different (p=0.008) from a comparable group of patients
that received aspirin only in previous trials and of whom 42/185 (22.7%) experienced
coronary artery aneurysms.10,11,12 All patients in the GAMMAGARD (immune globulin)
trial received concomitant aspirin therapy and none experienced hypersensitivity-type
reactions (urticaria, bronchospasm or generalized anaphylaxis).13
Several studies have documented the efficacy of intravenous gammaglobulin in
reducing the incidence of coronary artery abnormalities resulting from Kawasaki
syndrome.10-12, 14-17

DOSAGE AND ADMINISTRATION

Primary Immunodeficiency Diseases

For patients with primary immunodeficiencies, monthly doses of approximately
300-600 mg/kg infused at 3 to 4 week intervals are commonly used.42,43
As there are significant differences in the half-life of IgG among patients
with primary immunodeficiency, the frequency and amount of immunoglobulin therapy
may vary from patient to patient. The proper amount can be determined by monitoring
clinical response. The minimum serum concentration of IgG necessary for protection
varies among patients and has not been established by controlled clinical trials

B-cell Chronic Lymphocytic Leukemia (CLL)

For patients with hypogammaglobulinemia and/or recurrent bacterial infections due to B-cell Chronic Lymphocytic Leukemia, a dose of 400 mg/kg every 3 to 4 weeks is recommended.

Kawasaki Syndrome

For patients with Kawasaki syndrome, either a single 1 g/kg dose or a dose
of 400 mg/kg for four consecutive days beginning within seven days of the onset
of fever, administered concomitantly with appropriate aspirin therapy (80-100
mg/kg/day in four divided doses) is recommended.44

Idiopathic Thrombocytopenic Purpura (ITP)

For patients with acute or chronic Idiopathic Thrombocytopenic Purpura, a dose
of 1 g/kg is recommended. The need for additional doses can be determined by
clinical response and platelet count. Up to three separate doses may be given
on alternate days if required.

No prospective data are presently available to identify a maximum safe dose,
concentration, and rate of infusion in patients determined to be at increased
risk of acute renal failure. In the absence of prospective data, the recommended
doses should not be exceeded and the concentration and infusion rate selected
should be the minimum level practicable. Reduction in dose, concentration, and/or
rate of administration in patients at risk of acute renal failure has been proposed
in the literature in order to reduce the risk of acute renal failure.45

Reconstitution: Use Aseptic Technique

When reconstitution is performed aseptically outside of a sterile laminar air flow hood, administration should begin as soon as possible, but not more than 2 hours after reconstitution. When reconstitution is performed aseptically in a sterile laminar air flow hood, the reconstituted product may be either maintained in the original glass container or pooled into VIAFLEX bags and stored under constant refrigeration (2-8°C), for up to 24 hours. (The date and time of reconstitution/pooling should be recorded). If these conditions are not met, sterility of the reconstituted product cannot be maintained. Partially used vials should be discarded.

5. Remove protective covering from the spike at one end of the transfer device
(Fig. 1)

6. Place the diluent bottle on a flat surface and, while holding the bottle to prevent slipping, insert the spike of the transfer device perpendicularly through the center of the bottle stopper.

7. Press down firmly so that the transfer device fits snugly against the diluent bottle (Fig. 2).

Caution: Failure to use center of stopper may result in dislodging the
stopper.

8. Remove the protective covering from the other end of the transfer device. Hold diluent bottle to prevent slipping.

9. Hold concentrate bottle firmly and at an angle of approximately 45 degrees. Invert the diluent bottle with the transfer device at an angle complementary to the concentrate bottle (approximately 45 degrees) and firmly insert the transfer device into the concentrate bottle through the center of the rubber stopper (Fig. 3).

Note: Invert the diluent bottle with attached transfer device rapidly into
the concentrate bottle in order to avoid loss of diluent.

Caution: Failure to use center of stopper may result in dislodging the
stopper and loss of vacuum.

10. The diluent will flow into the concentrate bottle quickly. When diluent
transfer is complete, remove empty diluent bottle and transfer device from concentrate
bottle. Discard transfer device after single use. 11. Thoroughly wet the dried
material by tilting or inverting and gently rotating the bottle (Fig. 4). Do
not shake. Avoid foaming.

12. Repeat gentle rotation as long as undissolved product is observed.

B. 10% Solution

Follow steps 1-4 as previously described in A.

5. To prepare a 10% solution, reconstitute with the appropriate volume of diluent as indicated in Table 2, which indicates the volume of diluent required for a 5% or 10% concentration. Using aseptic technique, draw the required volume of diluent into a sterile hypodermic syringe and needle. Discard the filled syringe.

6. Using the residual diluent in the diluent vial, follow steps 5-12 as previously
described in A

Table 2: Required Diluent Volume

Concentration

2.5 g bottle

5 g bottle

10 g bottle

5%

50 mL

96 mL

192 mL

10%

25 mL

48 mL

96 mL

Rate of Administration

It is recommended that initially a 5% solution be infused at a rate of 0.5
mL/kg/Hr. If infusion at this rate and concentration causes the patient no distress,
the administration rate may be gradually increased to a maximum rate of 4 mL/kg/Hr
for patients with no history of adverse reactions to IGIV and no significant
risk factors for renal dysfunction or thrombotic complications. Patients who
tolerate the 5% concentration at 4 mL/kg/Hr can be infused with the 10% concentration
starting at 0.5 mL/kg/Hr. If no adverse effects occur, the rate can be increased
gradually up to a maximum of 8 mL/kg/Hr. In general, it is recommended that
patients beginning therapy with IGIV or switching from one IGIV product to another
be started at the lower rates of infusion and should be advanced to the maximal
rate only after they have tolerated several infusions at intermediate rates
of infusion. It is important to individualize rates for each patient. As noted
in the WARNINGSsection, patients who
have underlying renal disease or who are judged to be at risk of developing
thrombotic events should not be infused rapidly with any IGIV product.

Although there are no prospective studies demonstrating that any concentration
or rate of infusion is completely safe, it is believed that risk may be decreased
at lower rates of infusion.45 Therefore, as a guideline, it is recommended
that these patients who are judged to be at risk of renal dysfunction or thrombotic
complications be gradually titrated up to a more conservative maximal rate of
less than 3.3 mg/ kg/min ( < 2mL/kg/Hr of a 10% solution or < 4mL/kg/Hr
of a 5% solution).

It is recommended that antecubital veins be used especially for 10% solutions,
if possible. This may reduce the likelihood of the patient experiencing discomfort
at the infusion site (see ADVERSE REACTIONS).

A rate of administration which is too rapid may cause flushing and changes in pulse rate and blood pressure. Slowing or stopping the infusion usually allows the symptoms to disappear promptly.

Drug Interactions

Admixtures of GAMMAGARD S/D, Immune Globulin Intravenous (Human), with other drugs and intravenous solutions have not been evaluated. It is recommended that GAMMAGARD S/D (immune globulin) be administered separately from other drugs or medications which the patient may be receiving. The product should not be mixed with Immune Globulin Intravenous (Human) from other manufacturers. Antibodies in immune globulin preparations may interfere with patient responses to live vaccines, such as those for measles, mumps, and rubella. The immunizing physician should be informed of recent therapy with Immune Globulin Intravenous (Human) so that appropriate precautions can be taken.

Administration

GAMMAGARD S/D (immune globulin) should be administered as soon after reconstitution as possible,
or as described in the DOSAGE AND ADMINISTRATION.

The reconstituted material should be at room temperature during administration.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Reconstituted material should be a clear to slightly opalescent and colorless
to pale yellow solution. Do not use if particulate matter and/or discoloration
is observed.

Follow directions for use which accompany the administration set provided.
If another administration set is used, ensure that the set contains a similar
filter.

HOW SUPPLIED

GAMMAGARD S/D (immune globulin) is supplied in 2.5 g (NDC number 0944-2620-02), 5 g (NDC number 0944-2620-03), or 10 g (NDC number 0944-2620-04) single use bottles. Each bottle of GAMMAGARD S/D (immune globulin) is furnished with a suitable volume of Sterile Water for Injection, USP, a transfer device and an administration set which contains an integral airway and a 15 micron filter.

Storage

GAMMAGARD S/D (immune globulin) is to be stored at a temperature not to exceed 25°C (77°F). Freezing should be avoided to prevent the diluent bottle from breaking.